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Effects of sarah/nebula knockdown on Aβ42-induced phenotypes during Drosophila development

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Abstract

The Down syndrome critical region 1 (DSCR1), a Down syndrome-associated protein, is an endogenous inhibitor of the Ca2+-dependent phosphatase calcineurin. It has been also suggested to be associated with Alzheimer’s disease (AD) but the role of DSCR1 in the pathogenesis of AD still remains controversial. In this paper, we investigated the effects of knockdown of sarah (sra), a Drosophila DSCR1 ortholog, on the Aβ42-induced developmental phenotypes of Drosophila. Knockdown of sra showed detrimental effects on the rough eye phenotype and survival of Aβ42-expressing flies without altering the Aβ42 accumulation. Furthermore, the knockdown of sra increased glial cell numbers in the larval brains and its susceptibility to oxidative stress. Overexpression of an active form of calcineurin produced similar results to sra knockdown as they both exacerbated the Aβ42-induced rough eye phenotype. However, sra knockdown did not alter apoptosis or c-Jun N-terminal kinase activation in Aβ42-expressing flies. In conclusion, our results suggest that sra does play an important role in Aβ42-induced developmental defects in Drosophila without affecting its stress responses.

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Abbreviations

Aβ42 :

Amyloid-β-42

AD :

Alzheimer’s disease

DS :

Down syndrome

DSCR1 :

Down syndrome critical region 1

Sra :

Sarah

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Acknowledgments

This paper was supported by Konkuk University in 2013.

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    1. Department of Biological Sciences, Konkuk University, Seoul, 05029, Republic of Korea

      Se Min Bang, Soojin Lee, Haemin Jeong, Yoon Ki Hong, Jang Ho Lee, Soojin Hwang, Yoon Seok Suh, Kyungho Lee & Kyoung Sang Cho

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    1. Se Min Bang
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    Correspondence to Kyoung Sang Cho.

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    Se Min Bang and Soojin Lee have contributed equally to this work.

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    Bang, S.M., Lee, S., Jeong, H. et al. Effects of sarah/nebula knockdown on Aβ42-induced phenotypes during Drosophila development. Genes Genom 38, 479–487 (2016). https://doi.org/10.1007/s13258-016-0407-5

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